HRP20121068T1 - Inhibitori ciklopropil polimeraze - Google Patents
Inhibitori ciklopropil polimeraze Download PDFInfo
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- HRP20121068T1 HRP20121068T1 HRP20121068AT HRP20121068T HRP20121068T1 HR P20121068 T1 HRP20121068 T1 HR P20121068T1 HR P20121068A T HRP20121068A T HR P20121068AT HR P20121068 T HRP20121068 T HR P20121068T HR P20121068 T1 HRP20121068 T1 HR P20121068T1
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- Prior art keywords
- compound
- formula
- hydrogen
- group
- alkyl
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title claims 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 36
- 229910052739 hydrogen Inorganic materials 0.000 claims 22
- 239000001257 hydrogen Substances 0.000 claims 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 10
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims 8
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims 8
- 150000002431 hydrogen Chemical class 0.000 claims 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 5
- 125000006239 protecting group Chemical group 0.000 claims 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 4
- 238000006243 chemical reaction Methods 0.000 claims 4
- 229940104302 cytosine Drugs 0.000 claims 4
- 230000032050 esterification Effects 0.000 claims 4
- 238000005886 esterification reaction Methods 0.000 claims 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 229940035893 uracil Drugs 0.000 claims 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 3
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 claims 2
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 claims 2
- 125000001475 halogen functional group Chemical group 0.000 claims 2
- 125000001624 naphthyl group Chemical group 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- -1 triphosphate ester Chemical class 0.000 claims 2
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 claims 1
- 101100439662 Arabidopsis thaliana CHR5 gene Proteins 0.000 claims 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 claims 1
- 230000000840 anti-viral effect Effects 0.000 claims 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- ITVPBBDAZKBMRP-UHFFFAOYSA-N chloro-dioxido-oxo-$l^{5}-phosphane;hydron Chemical compound OP(O)(Cl)=O ITVPBBDAZKBMRP-UHFFFAOYSA-N 0.000 claims 1
- 229940125890 compound Ia Drugs 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 238000010511 deprotection reaction Methods 0.000 claims 1
- 150000005690 diesters Chemical class 0.000 claims 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001041 indolyl group Chemical group 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
- 235000011178 triphosphate Nutrition 0.000 claims 1
- 239000001226 triphosphate Substances 0.000 claims 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 claims 1
- 229940045145 uridine Drugs 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/073—Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
Claims (17)
1. Spoj sa formulom I:
[image]
uključujući njegove bilo koje moguće stereoizomere, naznačen time da:
R2 je vodik ili C1-C4alkil;
R3 i R4 su neovisno odabrani iz skupine koja sadrži vodik, -C(=O)R5, i -C(=O)CHR6-NH2; ili
R3 je vodik i R4 je monofosfatni-, difosfatni-, ili trifosfatni ester; ili R3 je vodik, -C(=O)CHR5, ili -C(=O)CHR6-NH2 i R4 je skupina sa formulom
[image]
svaki R5 je neovisno odabran iz skupine koja sadrži vodik, C1-C6alkil, i C3-C7cikloalkil;
R6 je vodik ili C1-C6alkil;
R7 je fenil, proizvoljno supstituiran sa 1, 2 ili 3 supstituenta koji su svaki neovisno odabrani od halo, C1-C6alkila, C3-C6alkenila, C1-C6alkoksi, hidroksi, i amino, ili R7 je naftil; ili R7 je indolil;
R8 je vodik, C1-C6alkil, benzil;
R8' je vodik, C1-C6alkil, benzil; ili
i R8' zajedno sa atomom ugljika na koji su vezani tvori C3-C7cikloalkil;
R9 je C1-C6alkil, benzil, ili fenil, pri čemu navedeni fenil može biti proizvoljno supstituiran sa 1, 2 ili 3 supstituenta koji su svaki neovisno odabrani od hidroksi, C1-C6alkoksi, amino, mono- i diC1-C6alkilamino;
pod uvjetom da R2, R3 i R4 nisu svi vodik;
ili njihove farmaceutski prihvatljive soli ili solvati.
2. Spoj prema zahtjevu 1, naznačen time da R2 je vodik.
3. Spoj prema zahtjevu 1, naznačen time da R3 i R4 su vodik.
4. Spoj prema bilo kojem od zahtjeva 1- 2, naznačen time da R3 je vodik i R4 je skupina sa formulom
[image]
5. Spoj prema bilo kojem od zahtjeva 1 do 2 ili zahtjevu 4, naznačen time da R7 je fenil, proizvoljno supstituiran sa halo, ili C1-C6alkilom, ili R7 je naftil.
6. Spoj prema bilo kojem od zahtjeva 1 do 2 ili zahtjevima 4 ili 5, naznačen time da R8 je vodik, i R8' je vodik ili C1-C6alkil.
7. Spoj prema bilo kojem od zahtjeva 1 do 2 ili zahtjevima 4 ili 5, naznačen time da jedan od R3 i R4 je -C(=O)R5, a drugi od R3 i R4 je vodik; ili pri čemu oba R3 i R4 su -C(=O)R5; te pri čemu R5 je C1-C6alkil.
8. Spoj prema zahtjevu 7 naznačen time da R5 je izopropil.
9. Spoj prema bilo kojem od zahtjeva 1 do 2 ili zahtjevima 4 do 8, naznačen time da R9 je C1-C6alkil ili benzil.
10. Spoj prema zahtjevu 1, naznačen time da spoj ima formulu:
[image]
11. Spoj prema zahtjevu 10, naznačen time da je navedeni spoj u slobodnom obliku.
12. Farmaceutski pripravak naznačen time da sadrži anti-virusno učinkovitu količinu spoja sa formulom I kako je definirano u bilo kojem od zahtjeva 1-11 i farmaceutski prihvatljiv nosač.
13. Spoj sa formulom I, kako je definirano u bilo kojem od zahtjeva 1-11, kao i spoj sa formulom I pri čemu R2, R3 i R4 su svi vodik, naznačen time da je za uporabu kao inhibitor HCV.
14. Spoj sa formulom I, za uporabu kao inhibitor HCV, prema zahtjevu 13, naznačen time da u spoju sa formulom I, su R2, R3 i R4 svi vodik.
15. Spoj sa formulom I, za uporabu kao inhibitor HCV, prema zahtjevu 14, naznačen time da je navedeni spoj u slobodnom obliku.
16. Kombinacija naznačena time da sadrži spoj sa formulom I, kao i spoj sa formulom I pri čemu R2, R3 i R4 su svi vodik, sa dodatnim inhibitorom HCV.
17. Postupak za dobivanje spoja sa formulom I, kako je definirano u bilo kojem od zahtjeva 1 do 11, naznačen time da se
(a) priprema spoj sa formulom I pri čemu R3 i R4 su oba vodik, ovdje prikazano sa formulom I-a, pomoću reakcije konverzije uracila u citozin od 2'-deoksi-2'-spirociklopropil uridina 1f u odgovarajući 2'-deoksi-2'-spirociklopropil citidin 1g, nakon čega slijedi uklanjanje zaštitnih skupina PG da se dobije spoj I-a:
[image]
(b) priprema spoj sa formulom I pri čemu R3 je vodik i R4 je
[image]
pomoću reakcije spoja I-a sa fosforokloridatom 2a u prisutnosti baze te se dobiva fosforamidat I-b:
[image]
(c) priprema spoj sa formulom I pri čemu R3 je vodik i R4 je -C(=O)R5 ili -C(=O)CHR6-NH2, ovdje prikazan sa R4a i navedenim spojem sa formulom I-c; ili R3 i R4 neovisno jedan od drugoga su -C(=O)R5 ili -C(=O)CHR6-NH2, nadalje predstavljen sa R3a i odgovarajućim R4a , te navedenim spojem sa formulom I-d; te pri čemu amino skupina u -C(=O)CHR6-NH2 može biti zaštićena sa amino zaštitnom skupinom koja može naknadno biti uklonjena;
pomoću selektivne zaštite 5'-hidroksi skupine u intermedijer 3a čime se dobiva intermedijer 3b, koji se zatim esterificira u intermedijer 3c, te se zatim provodi konverzija uracila u citozin u intermedijer 3d; te se za ovaj posljednji provodi uklanjanje zaštite u 3'-monoester I-c; ili pomoću esterifikacije iz 5'-hidroksi u I-c do spoja I-d; ili
pomoću selektivne esterifikacije 5'-hidroksi skupine u intermedijer 3a, te se stoga uvodi skupina R4a što dovodi do intermedijera 3e,a intermedijer 3e se naknadno esterificira sa različitom kiselinom te se uvodi skupina R3a, što dovodi do di-ester intermedijera 3f, koji se podvrgava konverziji uracila u citozin, da se dobije spoj I-d:
[image]
(d) priprema spoj sa formulom I pri čemu R3 je vodik i R4 je R4a kako je gore navedeno, a navedeni spoj prikazan je sa formulom I-e, pomoću zaštite slobodnog hidroksi u intermedijeru 3b sa hidroksi zaštitnom skupinom koja se selektivno cijepa prema drugoj hidroksi zaštitnoj skupini što rezultira sa intermedijerom 4a; te uklanjanjem 5'-hidroksi zaštitne skupine što dovodi do intermedijera 4b; te esterifikacije dobivenog intermedijera u intermedijer 4c; te podvrgavanja zadnjeg konverziji uracila u citozin da se tako dobije 4'-hidroksi zaštićeni derivat citidina 4d, kojemu se uklanja zaštita da se dobiju spojevi I-e; kako je prikazano u slijedećoj shemi, pri čemu skupina PGa ima ista značenja kao PG, ali je tako odabrana da se selektivno cijepa prema skupini PG:
[image]
(e) spoj sa formulom I pri čemu R3a i R4a su isti, te su kako je gore navedeno, a navedeni spoj je prikazan formulom I-f, priprema pomoću esterifikacije obje hidroksi skupine u intermedijeru 3a:
[image]
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08159396 | 2008-07-01 | ||
| EP08171005 | 2008-12-08 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20121068T1 true HRP20121068T1 (hr) | 2013-01-31 |
Family
ID=41095413
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20121068AT HRP20121068T1 (hr) | 2008-07-01 | 2012-12-27 | Inhibitori ciklopropil polimeraze |
Country Status (29)
| Country | Link |
|---|---|
| US (1) | US8431588B2 (hr) |
| EP (1) | EP2141172B1 (hr) |
| JP (1) | JP5624029B2 (hr) |
| KR (1) | KR20110038683A (hr) |
| CN (2) | CN102083845B (hr) |
| AP (1) | AP2010005505A0 (hr) |
| AR (1) | AR072428A1 (hr) |
| AU (1) | AU2009266004B2 (hr) |
| BR (1) | BRPI0913643A2 (hr) |
| CA (1) | CA2729316A1 (hr) |
| CL (1) | CL2010001634A1 (hr) |
| CO (1) | CO6321255A2 (hr) |
| DK (1) | DK2141172T3 (hr) |
| EA (1) | EA022754B1 (hr) |
| EC (1) | ECSP10010725A (hr) |
| ES (1) | ES2396803T3 (hr) |
| HK (1) | HK1226080A1 (hr) |
| HR (1) | HRP20121068T1 (hr) |
| IL (1) | IL209932A (hr) |
| MX (1) | MX2010014493A (hr) |
| NI (1) | NI201000231A (hr) |
| PL (1) | PL2141172T3 (hr) |
| PT (1) | PT2141172E (hr) |
| SI (1) | SI2141172T1 (hr) |
| SV (1) | SV2010003779A (hr) |
| TW (1) | TW201012814A (hr) |
| UY (1) | UY31950A (hr) |
| WO (1) | WO2010000459A1 (hr) |
| ZA (1) | ZA201009294B (hr) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20200028511A (ko) * | 2008-09-08 | 2020-03-16 | 사우디 아람코 테크놀로지스 컴퍼니 | 폴리카보네이트 폴리올 조성물 |
| UY32099A (es) | 2008-09-11 | 2010-04-30 | Enanta Pharm Inc | Inhibidores macrocíclicos de serina proteasas de hepatitis c |
| TW201201815A (en) * | 2010-05-28 | 2012-01-16 | Gilead Sciences Inc | 1'-substituted-carba-nucleoside prodrugs for antiviral treatment |
| AU2011352145A1 (en) | 2010-12-30 | 2013-07-18 | Abbvie Inc. | Phenanthridine macrocyclic hepatitis C serine protease inhibitors |
| MX2013007677A (es) | 2010-12-30 | 2013-07-30 | Abbvie Inc | Inhibidores macrociclicos de serina proteasa de hepatitis. |
| US10201584B1 (en) | 2011-05-17 | 2019-02-12 | Abbvie Inc. | Compositions and methods for treating HCV |
| JP5845841B2 (ja) | 2011-11-18 | 2016-01-20 | 東芝ライテック株式会社 | 照明制御装置 |
| MD20140094A2 (ro) | 2012-02-14 | 2015-03-31 | University Of Georgia Research Foundation, Inc. | Spiro [2.4]heptani pentru tratamentul infecţiilor cauzate de Flaviviridae |
| EP3089757A1 (en) | 2014-01-03 | 2016-11-09 | AbbVie Inc. | Solid antiviral dosage forms |
| UA124966C2 (uk) | 2015-03-06 | 2021-12-22 | Атеа Фармасеутікалс, Інк. | <font face="Symbol">b</font>-D-2'-ДЕЗОКСИ-2'-<font face="Symbol">a</font>-ФТОР-2'-<font face="Symbol">b</font>-C-ЗАМІЩЕНІ-2-МОДИФІКОВАНІ-N<sup>6</sup>-ЗАМІЩЕНІ ПУРИНОВІ НУКЛЕОТИДИ ДЛЯ ЛІКУВАННЯ ВИКЛИКАНИХ HCV ЗАХВОРЮВАНЬ |
| RU2590952C1 (ru) * | 2015-05-26 | 2016-07-10 | Вячеслав Энгельсович Семёнов | Средство гепатопротекторного действия |
| LU100724B1 (en) | 2016-07-14 | 2018-07-31 | Atea Pharmaceuticals Inc | Beta-d-2'-deoxy-2'-alpha-fluoro-2'-beta-c-substituted-4'-fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection |
| EP3865136A1 (en) | 2016-09-07 | 2021-08-18 | ATEA Pharmaceuticals, Inc. | 2'-substituted-n6-substituted purine nucleotides for corona virus treatment |
| KR20230151050A (ko) | 2017-02-01 | 2023-10-31 | 아테아 파마슈티컬즈, 인크. | C형 간염 바이러스를 치료하기 위한 뉴클레오티드 헤미-술페이트 염 |
| TW202012001A (zh) | 2018-04-10 | 2020-04-01 | 美商亞堤製藥公司 | C型肝炎病毒(hcv)感染硬化之患者的治療 |
| US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK0727419T3 (da) | 1992-12-29 | 2002-06-10 | Abbott Lab | Mellemprodukter til fremstilling af forbindelser, som inhiberer retroviral protease |
| IL110752A (en) * | 1993-09-13 | 2000-07-26 | Abbott Lab | Liquid semi-solid or solid pharmaceutical composition for an HIV protease inhibitor |
| US5559158A (en) | 1993-10-01 | 1996-09-24 | Abbott Laboratories | Pharmaceutical composition |
| IL111991A (en) | 1994-01-28 | 2000-07-26 | Abbott Lab | Liquid pharmaceutical composition of HIV protease inhibitors in organic solvent |
| US6037157A (en) | 1995-06-29 | 2000-03-14 | Abbott Laboratories | Method for improving pharmacokinetics |
| GB0114286D0 (en) * | 2001-06-12 | 2001-08-01 | Hoffmann La Roche | Nucleoside Derivatives |
| JP2005533817A (ja) * | 2002-06-28 | 2005-11-10 | イデニクス（ケイマン）リミテツド | フラビウィルス科ウィルス感染治療用の修飾２′および３′−ヌクレオシドプロドラッグ |
| DK1628685T3 (da) * | 2003-04-25 | 2011-03-21 | Gilead Sciences Inc | Antivirale phosphonatanaloge |
| ES2327252T3 (es) * | 2004-08-23 | 2009-10-27 | F. Hoffmann-La Roche Ag | 4'-azido nucleosidos antivirales. |
| WO2008043704A1 (en) * | 2006-10-10 | 2008-04-17 | Medivir Ab | Hcv nucleoside inhibitor |
-
2009
- 2009-06-30 UY UY0001031950A patent/UY31950A/es unknown
- 2009-06-30 AR ARP090102442A patent/AR072428A1/es not_active Application Discontinuation
- 2009-06-30 TW TW098121932A patent/TW201012814A/zh unknown
- 2009-07-01 CA CA2729316A patent/CA2729316A1/en not_active Abandoned
- 2009-07-01 EA EA201170118A patent/EA022754B1/ru not_active IP Right Cessation
- 2009-07-01 US US12/999,263 patent/US8431588B2/en not_active Expired - Fee Related
- 2009-07-01 PL PL09008634T patent/PL2141172T3/pl unknown
- 2009-07-01 JP JP2011515237A patent/JP5624029B2/ja not_active Expired - Fee Related
- 2009-07-01 BR BRPI0913643A patent/BRPI0913643A2/pt not_active IP Right Cessation
- 2009-07-01 KR KR1020117002345A patent/KR20110038683A/ko not_active Application Discontinuation
- 2009-07-01 DK DK09008634.9T patent/DK2141172T3/da active
- 2009-07-01 PT PT90086349T patent/PT2141172E/pt unknown
- 2009-07-01 ES ES09008634T patent/ES2396803T3/es active Active
- 2009-07-01 EP EP09008634A patent/EP2141172B1/en active Active
- 2009-07-01 SI SI200930467T patent/SI2141172T1/sl unknown
- 2009-07-01 AU AU2009266004A patent/AU2009266004B2/en not_active Ceased
- 2009-07-01 MX MX2010014493A patent/MX2010014493A/es active IP Right Grant
- 2009-07-01 CN CN200980125579.1A patent/CN102083845B/zh not_active Expired - Fee Related
- 2009-07-01 WO PCT/EP2009/004748 patent/WO2010000459A1/en active Application Filing
- 2009-07-01 AP AP2010005505A patent/AP2010005505A0/xx unknown
- 2009-07-01 CN CN201610033092.2A patent/CN105693794A/zh active Pending
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2010
- 2010-12-12 IL IL209932A patent/IL209932A/en not_active IP Right Cessation
- 2010-12-22 SV SV2010003779A patent/SV2010003779A/es not_active Application Discontinuation
- 2010-12-23 CO CO10161808A patent/CO6321255A2/es not_active Application Discontinuation
- 2010-12-23 NI NI201000231A patent/NI201000231A/es unknown
- 2010-12-23 ZA ZA2010/09294A patent/ZA201009294B/en unknown
- 2010-12-29 EC EC2010010725A patent/ECSP10010725A/es unknown
- 2010-12-30 CL CL2010001634A patent/CL2010001634A1/es unknown
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2012
- 2012-12-27 HR HRP20121068AT patent/HRP20121068T1/hr unknown
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2016
- 2016-12-15 HK HK16114266A patent/HK1226080A1/zh unknown
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